title: QSAR models for anti-androgenic effect--a preliminary study.
abstract: Three modelling systems (MultiCase®, LeadScope® and MDL® QSAR) were used for construction of androgenic receptor antagonist models. There were 923-942 chemicals in the training sets. The models were cross-validated (leave-groups-out) with concordances of 77-81%, specificity of 78-91% and sensitivity of 51-76%. The specificity was highest in the MultiCase® model and the sensitivity was highest in the MDL® QSAR model. A complementary use of the models may be a valuable tool when optimizing the prediction of chemicals for androgenic receptor antagonism. When evaluating the fitness of the model for a particular application, balance of training sets, domain definition, and cut-offs for prediction interpretation should also be taken into account. Different descriptors in the modelling systems are illustrated with hydroxyflutamide and dexamethasone as examples (a non-steroid and a steroid anti-androgen, respectively). More research concerning the mechanism of anti-androgens would increase the possibility for further optimization of the QSAR models. Further expansion of the basis for the models is in progress, including the addition of more drugs.
authors.affiliation: Department of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Søborg, Denmark. gunje@food.dtu.dk
authors.forename: G E
authors.initials: GE
authors.lastname: Jensen
authors.forename: N G
authors.initials: NG
authors.lastname: Nikolov
authors.forename: E B
authors.initials: EB
authors.lastname: Wedebye
authors.forename: T
authors.initials: T
authors.lastname: Ringsted
authors.forename: J R
authors.initials: JR
authors.lastname: Niemela
mesh_terms: D000726:Androgen Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus / Q000502:physiology; D003907:Dexamethasone / Q000737:chemistry / Q000494:pharmacology; D005485:Flutamide / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D011944:Receptors, Androgen; C014290:hydroxyflutamide; D005485:Flutamide; D003907:Dexamethasone